ABSTRACT
The "Noah's Ark" project, afoot at M.V. Lomonosov Moscow State University since 2015 and aimed at studying biodiversity, is the largest ongoing Russian project in life sciences. During its implementation, several hundred new species have been described; a comprehensive genetic and biochemical characterization of these species, as well as that of the pre-existing specimens in Moscow University's collections, has been performed. A consolidated IT system intended to house the knowledge generated by the project has been developed. Here, we summarize the investigations around the Moscow University classical biocollections which have taken place within the framework of the project and discuss future promise and the outlook for these collections.
ABSTRACT
Urokinase-type plasminogen activator (uPA) plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program), postprocessing (DISCORE program), direct generalized docking (FLM program), and the application of the quantum chemical calculations (MOPAC package), search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 µM.
